Sci. Pharm., Volume 87, Issue 1 (March 2019) – 7 articles

The article presents the synthesis of 2-arylimino-4-methyl-2,3-dihydro-1,3-thiazoles via Hantzsch reaction of thioureas and 3-chloropentane-2,4-dione or ethyl 2-chloro-3-oxobutanoate. The structure of synthesized compounds was confirmed by LCMS, ¹H, and ¹³C NMR spectra. Cardioprotective activity of synthesized thiazole derivatives were studied in vitro on the isolated rings of the thoracic aorta of laboratory rats. Based on pharmacological studies, the tested compounds possessed a moderate to high cardioprotective effect. A prospective 1-[2-(4-methoxyphenylimino)-4-methyl-3-(4-methylpiperazine-1-yl)-2,3-dihydro-1,3-thiazole-5-yl] ethan-1-one hydrochloride 4c was identified. The mentioned compound has delayed the development of constrictor responses of isolated rings of the thoracic rat aorta and exceeds the activity of L-carnitine by 18.2% and meldonium by 12.9%. The compound 4c may be proposed as a potential cardioprotective agent for in-depth pharmacological studies. Full article

Treatment of certain central nervous system disorders, including different types of cerebral malignancies, is limited by traditional oral or systemic administrations of therapeutic drugs due to possible serious side effects and/or lack of the brain penetration and, therefore, the efficacy of the drugs is diminished. During the last decade, several new technologies were developed to overcome barrier properties of cerebral capillaries. This review gives a short overview of the structural elements and anatomical features of the blood–brain barrier. The various in vitro (static and dynamic), in vivo (microdialysis), and in situ (brain perfusion) blood–brain barrier models are also presented. The drug formulations and administration options to deliver molecules effectively to the central nervous system (CNS) are presented. Nanocarriers, nanoparticles (lipid, polymeric, magnetic, gold, and carbon based nanoparticles, dendrimers, etc.), viral and peptid vectors and shuttles, sonoporation and microbubbles are briefly shown. The modulation of receptors and efflux transporters in the cell membrane can also be an effective approach to enhance brain exposure to therapeutic compounds. Intranasal administration is a noninvasive delivery route to bypass the blood–brain barrier, while direct brain administration is an invasive mode to target the brain region with therapeutic drug concentrations locally. Nowadays, both technological and mechanistic tools are available to assist in overcoming the blood–brain barrier. With these techniques more effective and even safer drugs can be developed for the treatment of devastating brain disorders. Full article

Proteins play crucial roles in the transportation and distribution of therapeutic substances, including metal ions in living systems. Some metal ions can strongly associate, while others show low affinity towards proteins. Consequently, in the present work, the binding behaviors of Ca²⁺, Ba²⁺, Ag⁺, Ru³⁺, Cu²⁺ and Co²⁺ with bovine serum albumin (BSA) were screened. BSA and the metal ions were allowed to interact at physiological pH and their binding interactions were screened by using FT-IR spectroscopy. Spectra were collected by using hydrated films over a range of 4000–400 cm⁻¹. The interaction was demonstrated by a significant reduction in the spectral intensities of the amide I (C=O stretching) and amide II bands (C–N stretching coupled to NH bending) of the protein after complexation with metal ions. The binding interaction was further revealed by spectral shifting of the amide I band from 1651 cm⁻¹ (free BSA) to 1653, 1654, 1649, 1655, 1655, and 1654 cm⁻¹ for BSA–Ca²⁺, BSA–Ba²⁺, BSA–Ag⁺, BSA–Ru³⁺, BSA–Cu²⁺ and BSA–Co²⁺ complexes, respectively. The shifting of the amide I band was due to the interactions of metal ions with the O and N atoms of the ligand protein. Estimation of the secondary protein structure showed alteration in the protein conformation, characterized by a marked decrease (12.9–40.3%) in the α-helix accompanied by increased β-sheet and β-turn after interaction with the metal ions. The interaction results of this study were comparable with those reported in our previous investigation of metal ion–BSA interactions using affinity capillary electrophoresis (ACE), which has proven the accuracy of the FT-IR technique in the measurement of interactions between proteins and metal ions. Full article

Nigella sativa oil has been known to have potent anti-inflammatory activity. This research aimed to determine the anti-inflammation activity of Nigella sativa oil in a simple balm stick by topical application. The activity was checked using two methods: carrageenan-induced paw oedema and granuloma pouch on rats. The results showed that balm sticks which contained 10% Nigella sativa could overcome both acute and sub-acute inflammation showing by high oedema inhibition (60.64%), low leucocytes count (43.55% lower than control) as well as a notable TNF-α concentration (50% lower than control) on the inflamed area. In conclusion, topical application of a Nigella sativa balm stick was effective for both acute and sub-acute forms of inflammation. Full article

Berberis goudotii is an endemic Colombian plant found in the paramo ecosystem. It has been used in food preparation and as a medicinal plant for diverse treatments. Additionally, it is used as a mouthwash to strengthen the gums and combat throat irritations and periodontitis. The present research evaluated Berberis goudotii aerial parts extract and fractions antimicrobial activities. Ultrasonic-assisted extraction was used to attain total ethanol-water extract. Solid-liquid fractionation was used to obtain hexane fraction. The residue was dispersed in water and liquid-liquid fractionation was carried-out to acquire dichloromethane, butanol and water fractions. Preliminary phytochemical analysis was performed on total extract and phenol, polyphenol, flavonoid, and proanthocyanidin, while tannin content was quantified. Antimicrobial activity assessment was performed by agar diffusion method using disks and wells employing Ceftazidime as a positive control against Streptococcus mutans, Streptococcus sobrinus, Lactobacillus acidophilus, Lactobacillus casei, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum. Antimicrobial activity was determined as relative percentage inhibition (RPI), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Phenols (92.5 ± 7.7 mg GA/10 g), polyphenols (87.7 ± 8.1 mg PG/10 g) and tannins (44.1 ± 4.3 mg PG/10 g) were among the highest secondary metabolites observed. Total extract presented an MBC of 1.0 µg/µL against cariogenic bacteria (Streptococcus mutans and Streptococcus sobrinus) and 0.12 µg/µL against bacteria associated with periodontal disease (Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum). Butanol and hexane fractions showed antiperiodontal activity with MBC of 0.12 and 1.0 µg/µL, respectively. In conclusion, Berberis goudotii total extract demonstrated antimicrobial activity against cariogenic and periodontal microorganisms, on the other hand, hexane and butanol fractions displayed antiperiodontal activity. Full article

Usnic acid is known for its remarkable antimicrobial activity. The aim of this research was to formulate hydrogel of usnic acid and evaluate the antibacterial activity against Propionibacterium acne. Due to low solubility of usnic acid, solid dispersion was prepared using PVP K-30. In this study, intact usnic acid (UA) and usnic acid-solid dispersion (UA-SD) was formulated in hydrogel using several gelling agents: Aqupec HV-505, sodium alginate and HPMC K 100M. Concentration of each gelling agent was optimized for hydrogel base. All of hydrogel base showed homogenous gel, pH at range 5.37–6.33 and viscosity in range 259.07–10,759.00 cps. Hydrogel was prepared by dispersing 1% intact UA and 3% UA-SD in three different gelling agents. The hydrogel was evaluated for pH, viscosity, stability test for two months and microbiology test. The amount of usnic acid in hydrogel was determined by spectrophotometry UV-Vis. Hydrogel UA showed non-homogenous gel, while hydrogel usnic UA-SD was homogenous. The pH of all hydrogel was in range 5.5–6.4 and viscosity was 2,017.03–3,866.52 cps. All the hydrogel was stable and diameter inhibition of hydrogel was in a range 20–32 mm. The amount of usnic acid in hydrogel was in range 96.9–99.23%. In conclusion, hydrogel UA-SD is promising preparation in handling acne. Full article